USA: A recent phase 2 study has revealed that nipocalimab, an investigational treatment, demonstrates significant benefits in managing early-onset severe hemolytic disease of the fetus and newborn (HDFN). The study could transform the approach to treating pregnancies at high risk for this severe condition, offering hope for improved outcomes.
The researchers found that nipocalimab treatment either delayed or prevented fetal anemia and the need for intrauterine transfusions in pregnancies at high risk for early-onset severe hemolytic disease of the fetus and newborn, compared to historical benchmarks. The findings were published online in The New England Journal of Medicine.

In early-onset severe HDFN, a condition where the mother’s immune system attacks the fetus's red blood cells, the transplacental transfer of maternal antierythrocyte IgG alloantibodies results in fetal anemia. This often necessitates high-risk intrauterine transfusions to prevent fetal hydrops and potential fetal death. Traditionally, managing this condition has been challenging, and treatment options have been limited. Nipocalimab, an anti-neonatal Fc receptor blocker, reduces the transfer of IgG across the placenta and decreases maternal IgG levels.
Against the above background, Kenneth J. Moise, University of Texas at Austin, Austin, TX, and colleagues evaluated the administration of intravenous nipocalimab (30 or 45 mg per kilogram of body weight per week) from 14 to 35 weeks gestation in participants with pregnancies at high risk for recurrent early-onset severe hemolytic disease of the fetus and newborn in an international, open-label, single-group, phase 2 study.
The primary endpoint was a live birth at 32 weeks gestation or later without requiring intrauterine transfusions, evaluated against a historical benchmark where the rate was 0%. A clinically significant difference was set at 10%.
The study led to the following findings:
Live birth at 32 weeks gestation or later without intrauterine transfusions occurred in 54% of pregnancies in the study.
No cases of fetal hydrops occurred, and 46% of participants did not receive any antenatal or neonatal transfusions.
Six fetuses received an intrauterine transfusion: five fetuses at 24 weeks gestation or later and one fetus before a fetal loss at 22 weeks and five days gestation. Live births occurred in 12 pregnancies.
The median gestational age at delivery was 36 weeks and four days.
Of the 12 live-born infants, 1 received one exchange transfusion and one simple transfusion, and 5 received only simple transfusions.
Treatment-related decreases in the alloantibody titer and IgG level were observed in maternal samples and cord blood.
There were no unusual maternal or pediatric infections.
Serious adverse events were consistent with HDFN, pregnancy, or prematurity.
"Nipocalimab offers a promising new approach to managing early-onset severe hemolytic disease of the fetus and newborn. Its potential to delay or prevent severe complications represents a significant advancement in prenatal care, offering hope for better outcomes in high-risk pregnancies," the researchers concluded.
Reference:
Moise, Jr, K. J., et al. (2024) Nipocalimab in Early-Onset Severe Hemolytic Disease of the Fetus and Newborn. New England Journal of Medicine. doi.org/10.1056/NEJMoa2314466.